Compositions for controlling parasites on animals

ABSTRACT

The present invention relates to novel skin-friendly dermally applicable liquid formulations comprising a pyrethrin or pyrethroid and MGK 264 in a ratio of at least 1:20 and a further insecticide, preferably from the group of the neonicotinoids, for controlling parasitic arthropods on animals.

This application is a 371 of PCT/EP2004/004359, filed Apr. 24, 2004.

The present invention relates to novel compositions for controllingparasites on animals, which compositions comprise a pyrethrin orpyrethroid and MGK 264; if appropriate, the compositions comprise afurther insecticially and/or acaricidally active compound.

To apply active compounds, some of which are poorly water soluble, inthe form of dermally applicable liquid formulations, it is necessary toprepare homogeneous solutions or emulsions based on organic solvents andinsecticidally active compounds. For this purpose, the active compoundsare in most cases dissolved in organic solvents, such as isopropanol,2-butoxyethyl acetate or ethylene glycol diacetate, and, if appropriate,mixed with further additives. The preparation of such formulations isdescribed in U.S. Pat. No. 4,874,753, EP-A 137 627 and GB 2 135 886. Thedisadvantages of said systems are, for example when active compoundsfrom the class of the pyrethrins and pyrethroids, in particularα-cyanopyrethroids, are used, that they cause severe skin irritationsand, furthermore, have only a short long-term action. It is desirable toreplace these formulations by formulations which are skin-friendly andtoxicologically acceptable and have a long-term action of several weeks.

To overcome said disadvantage of, for example, the known pyrethroids andpyrethrins, AU-627 847 and EP-A 413 610 propose to dissolve these activecompounds in high-boiling solvents such as monopropyleneglycol whichadditionally also comprise natural skin-friendly oils such as pine oil,sunflower oil or soya oil. WO 91/13545 discloses that it is possible toprepare skin-friendly liquid formulations with good activity bydissolving said active compounds in amounts of >50% in aliphaticsolvents such as 2-(2-butoxyethoxy)ethanol or2-(2-methoxyethoxy)ethanol. The disadvantage of these formulations isthat they require the use of relatively large amounts of active compoundand that they also cause skin irritations in sensitive animal breeds. Toachieve an acceptable biological action using small amounts of activecompound, the U.S. Pat. No. 5,466,458 proposes the use of emulsionsbased on said active compounds with long-chain aliphatic amines oralcohols such as hexadecan-1-ol or 1-octadecylamine. The use oflong-chain amines has the disadvantage that they degrade said activecompounds over time. In most cases, the formulations based on long-chainalcohols have insufficient long-term action.

Furthermore, WO 01/35739 proposes to combine pyrethroids, in particularα-cyanopyrethroids, which are critical with respect to skin irritation,with polysiloxanes which additionally comprise quaternary ammoniumgroups. However, this elegant form of preparation has the disadvantagethat it requires the use of relatively large amounts of pyrethroid. Inmany cases, this fact may result in incompatibility with the targetanimal or the environment.

The literature states that synthetic or natural pyrethroids can becombined with organic synergists such as piperonyl butoxide (PBO),(2-(2-ethylhexyl)-3a,4,7,7a-tetrahydro-4,7-methano-1H-isoindole-1,3(2H)-dione(MGK 264), S,S,S-tributylphosphorotrithioate (DEF) or Synepirin [see,for example, JOURNAL OF ECONOMIC ENTOMOLOGY, (1994 August) 87 (4)879-84, 1994), JOURNAL OF ECONOMIC ENTOMOLOGY, (1987 August) 80 (4)728-32 or India Chemosphere, (November, 1997) Vol. 35, No. 10, pp.2365-2374. ISSN: 0045-6535, Japanese Journal of Sanitary Zoology, (1995)Vol. 46, No. 1, pp. 25-30. ISSN: 0424-7086. 1995 and also J ECONENTOMOL, (1987) 80 (6), 1117-1121. CODEN: JEENAI. ISSN: 0022-0493.1987)]. The literature mentioned above also states that the activity ofthe pyrethroid-containing preparations against adult fleas can beimproved by combining pyrethroids with said synergists in amounts offrom 1:5 to at most 1:20. The literature [see, for example, DEP.ENTOMOL., UNIV. GEORGIA, COASTAL PLAIN EXP. STN., TIFTON, GA. 31793 orIndia Chemosphere, (1998) 36/15 (3055-3060) 1998] states, that maximumimprovement of activity is achieved at a ratio of active compound tosynergist of 1:5 (for example in the case of permethrin/MGK-264 orfenvalerate/PBO).

Furthermore, it is known that shampoos comprising dipropylpyridine-2,5-dicarboxylate, MGK 264, piperonyl butoxide, and pyrethrinscan be used for controlling fleas on small animals [see, for example,Wang I.-H.; Moorman R.; Burleson J. I.-H. Wang, Journal of LiquidChromatography and Related Technologies, (1996) 19/20 (3293-3304)].

It is furthermore known that carbamates such as propoxur in combinationwith PPO and MGK 264 in ratios of 1.00:0.04:0.1 are suitable fortreating habitats (see, for example, the company prospectus from SanoBruns Enterprises Ltd. Israel, 1990 AO1N-047/44).

U.S. Pat. No. 0,124,306, 1999, describes combinations of imidaclopridand/or fipronil and/or pyrethroids for controlling pests in agriculture.Furthermore, EP-A-981 956 (U.S. Pat. No. 6,080,796) describes foamsbased on the abovementioned active compounds, and the patent applicationEP-A-981 955 (U.S. Pat. No. 6,033,731) describes polymer alloys preparedfrom suspensions or emulsions of the active compounds imidacloprid andpermethrin, for controlling parasites.

All of the preparation forms mentioned have the disadvantage that, in anacceptable application form, they are not suitable for controllingectoparasites, such as fleas, ticks and mosquitoes, for a duration of atleast three, but preferably four, weeks, and that they furthermorerequire the use of relatively large amounts of active compound.

It is an object of the present invention to provide compositionscomprising pyrethroids or pyrethrins, which compositions are suitablefor controlling parasites, preferably ectoparasites, on animals. Suchpreparations have high parasiticidal activity and are well tolerated bythe animal treated. In addition, good user compatibility andenvironmental compatibility are also important. It should be possible toproduce liquid preparations allowing the elegant spot-on application.

Surprisingly, this object is achieved by employing pyrethroids and/orpyrethrins, in particular α-cyanopyrethroids, in combination with thesynergist MGK 264 in amounts of at least 1:20, in contrast to currentteaching.

Surprisingly, using the ratios of at least 1:20 according to theinvention, a considerably improved target animal and user compatibilityand an enormous activity-enhancing synergistic effect are achieved.

Accordingly, the invention relates to compositions, comprising

-   a) at least one active compound from the compound class of the    pyrethroids and/or the compound class of the pyrethrins-   b) MGK 264    in a weight ratio of components a:b of at least 1:20,    and also-   c) if appropriate, further active compounds and-   d) if appropriate further auxiliaries and carriers.

In general, the pyrethrins are employed in combination with apyrethroid.

The compositions according to the invention are preferably fluid orliquid and are particularly highly suitable for preparing spot-on andpour-on formulations for use in parasite control on animals.

Suitable active compounds (component a) which are to be emphasized arethe pyrethrins and the pyrethroids, such as, for example: fenvalerate[α-cyano-3-phenoxybenzyl α-(p-Cl-phenyl)isovalerate], flumethrin[(α-cyano-4-fluoro-3-phenoxy)benzyl3-[2-4-chlorophenyl)-2-chlorovinyl]-2,2-dimethylcyclopropanecarboxylate]and its enantiomers and stereoisomers, cyfluthrin[(α-cyano-4-fluoro-3-phenoxy)benzyl2,2-dimethyl-3-2,2-dichlorovinyl)cyclopropanecarboxylate], permethrin[3-phenoxybenzylcis,trans-3-2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate],cypermethrin [α-cyano-3-phenoxybenzyl2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylate], deltamethrin[α-cyano-3-phenoxybenzylcis,trans-3-2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate],fluvalinate [2-cyano-3-phenoxybenzyl2-(2-chloro-α,α,α-trifluoro-p-toluido)-3-methylbutyrate]. Preference isgiven to using pyrethroids having acaricidal action. Particularlypreferred are the α-cyanopyrethroids, in particular the esters ofα-cyano-3-phenylbenzyl alcohols and 4-fluoro-L-cyano-3-phenoxybenzylalcohols. Among these, particular preference is given to flumethrin,cyfluthrin and β-cyfluthrin.

In the compositions according to the invention, the pyrethrins and/orpyrethroids are usually present in amounts of 0.01-20% by weight,preferably 0.05-5.0% by weight, particularly preferably 0.075-0.75% byweight, very particularly preferably 0.10-0.50% by weight, based in eachcase on the weight of the finished composition. In the case of sprayapplications, the concentrations are usually lower, namely preferably inthe range of from 0.02 to 0.1% by weight, particularly preferably 0.03to 0.1% by weight, very particularly preferably 0.03 to 0.075% byweight.

The ratio by weight of the amount of pyrethrin and/or pyrethroid to theamount of MGK 264 is at least 1:20 (here, “at least” means that theproportion of MGK 264 in the ratio to pyrethrin/pyrethroid may also behigher), preferably 1:30, particularly preferably 1:40. Usually, theratio is adjusted to be not more than 1:100, preferably 1:80,particularly preferably 1:60.

Of course, the compositions according to the invention may alsocomprise, as combination partners, further active compounds.

Preferred active compounds for combinations which may be mentioned areinsecticides used for controlling ectoparasitic arthropods, such asneonicotinoid insecticides, spinosyns, N-phenylpyrazoles, carbamates,phosphoric and phosphonic esters, growth inhibitors and also mixtures ofthese active compounds with one another. It is also possible to addfurther synergists. For the purpose of this application, synergists areto be understood as meaning compounds which for their part do not havethe desired activity but, as mixing partners, enhance the activity ofthe active compounds.

Neonicotinoid insecticides which may be mentioned are compounds of theformulae (I), (II) and (III):

in which

-   n represents 1 or 2,-   m represents 0, 1 or 2,-   Subst. represents one of the substituents listed above, preferably    halogen, particularly preferably chlorine,-   A represents a monofunctional group from the group consisting of    hydrogen, acyl, alkyl and aryl or represents a bifunctional group    which is attached to the radical Z;-   E represents an electron-withdrawing radical;-   X represents the radicals —CH═ or ═N—, where the radical —CH═ may be    attached instead of an H atom to the radical Z;-   Z represents a monofunctional group from the group consisting of    alkyl, —O—R, —S—R and

-   -   or represents a bifunctional group which is attached to the        radical A or the radical X.

Preference is given to compounds of the formulae (I), (II) and (III),where the radicals are as defined below:

-   A particularly preferably represents hydrogen and optionally    substituted radicals from the group consisting of C₁-C₈-acyl,    C₁-C₁₀-alkyl, C₆-C₁₀-aryl. A furthermore represents a bifunctional    group. Mention may be made of optionally substituted alkylene having    1-4, in particular 1-2, C atoms, suitable substituents being the    substituents listed further above, where the alkylene groups may be    interrupted by one or two identical or different heteroatoms from    the group consisting of N, O and S.-   A and Z together with the atoms to which they are attached may form    a saturated or unsaturated heterocyclic ring. The heterocyclic ring    may contain a further 1 or 2 identical or different heteroatoms    and/or hetero groups. Preferred heteroatoms are oxygen, sulphur or    nitrogen, and preferred hetero groups are N-alkyl groups, where the    alkyl of the N-alkyl group preferably contains 1 to 4, in particular    1 or 2, carbon atoms. Alkyl groups which may be mentioned are    methyl, ethyl, n- and i-propyl and n-, i- and t-butyl. The    heterocyclic ring contains 5 to 7, preferably 5 or 6, ring members.    -   Examples of the heterocyclic ring which may be mentioned are        pyrrolidine, piperidine, piperazine, hexamethyleneimine,        hexahydro-1,3,5-triazine and morpholine which, if appropriate,        may be substituted, preferably by methyl.-   E represents an electron-withdrawing radical; mention may be made in    particular of NO₂, CN, haloalkyl carbonyl, and in particular having    1-4 carbon atoms and 1 to 5 halogen atoms, such as, for example,    COCF₃.-   X represents —CH═ or —N═.-   Z represents optionally substituted radicals C₁-C₁₀-alkyl, —OR, —SR,    —NRR, where the substituents are preferably as defined under R.-   Z may, in addition to the abovementioned ring, together with the    atom to which it is attached and the radical

-   -   instead of X form a saturated or unsaturated heterocyclic ring.        The heterocyclic ring may contain a further 1 or 2 identical or        different heteroatoms and/or hetero groups. Preferred        heteroatoms are oxygen, sulphur or nitrogen, and preferred        hetero groups are N-alkyl groups, where the alkyl or N-alkyl        group preferably contains 1 to 4, in particular 1 or 2, carbon        atoms. Alkyl groups which may be mentioned are methyl, ethyl, n-        and i-propyl and n-, i- and t-butyl. The heterocyclic ring        contains 5 to 7, preferably 5 or 6, ring members.    -   Examples of the heterocyclic ring which may be mentioned are        pyrrolidine, piperidine, piperazine, hexamethyleneimine,        morpholine and N-methylpiperazme.

-   R represents hydrogen and also represents optionally substituted    radicals from the group consisting of acyl, alkyl, aryl, aralkyl,    heteroaryl, heteroarylalkyl.    -   Acyl radicals which may be mentioned are formyl, alkylcarbonyl,        arylcarbonyl, alkylsulphonyl, arylsulphonyl,        (alkyl)(aryl)phosphoryl, which for their part may be        substituted.    -   Alkyl groups which may be mentioned are C₁₋₁₀-alkyl, in        particular C₁₋₄-allyl, specifically methyl, ethyl, isopropyl,        sec- or tert-butyl, which for their part may be substituted.    -   Aryl groups which may be mentioned are phenyl and naphthyl, in        particular phenyl.    -   Aralkyl groups which may be mentioned are phenylmethyl and        phenethyl.    -   Heteroaryl groups which may be mentioned are heteroaryl groups        having up to 10 ring atoms and, as heteroatoms, N, O, S, in        particular N. Specific mention may be made of thienyl, furyl,        thiazolyl, imidazolyl, pyridyl, benzothiazolyl.    -   Heteroarylalkyl groups which may be mentioned are        heteroarylmethyl, heteroarylethyl having up to 6 ring atoms and,        as heteroatoms, N, O, S, in particular N.    -   Substituents which may be mentioned are, by way of example and        preferably:    -   alkyl having preferably 1 to 4, in particular 1 or 2, carbon        atoms, such as methyl, ethyl, n- and i-propyl and n-, i- and        t-butyl; alkoxy having preferably 1 to 4, in particular 1 or 2,        carbon atoms, such as methoxy, ethoxy, n- and i-propyloxy and        n-, i- and t-butyloxy, alkylthio having preferably 1 to 4, in        particular 1 or 2, carbon atoms, such as methylthio, ethylthio,        n- and i-propylthio and n-, i- and t-butylthio; haloalkyl having        preferably 1 to 4, in particular 1 or 2, carbon atoms and        preferably 1 to 5, in particular 1 to 3, halogen atoms, the        halogen atoms being identical or different and preferably being        fluorine, chlorine or bromine, in particular fluorine, such as        trifluoromethyl; hydroxyl; halogen, preferably fluorine,        chlorine, bromine and iodine, in particular fluorine, chlorine        and bromine; cyano; nitro; amino; monoalkyl- and dialkylamino        having preferably 1 to 4, in particular 1 or 2, carbon atoms per        alkyl group, such as methylamino, methylethylamino, n- and        i-propylamino and methyl-n-butylamino; carboxyl; carbalkoxy        having preferably 2 to 4, in particular 2 or 3, carbon atoms,        such as carbomethoxy and carboethoxy; sulpho (—SO₃H);        alkylsulphonyl having preferably 1 to 4, in particular 1 or 2,        carbon atoms, such as methylsulphonyl and ethylsulphonyl;        arylsulphonyl having preferably 6 or 10 aryl carbon atoms, such        as phenylsulphonyl, and also heteroarylamino and        heteroarylalkylamino, such as chloropyridylamino and        chloropyridylmethylamino.

Very particular preference is given to compounds of the formulae (I),(II) and (III) in which

-   N represents 1,-   m represents 0,-   Subst. represents chlorine,-   A represents hydrogen or C₁₋₃-alkyl,-   Z represents C₁₋₃-alkyl, —NH₂, —NH(C₁₋₃-alkyl) or —N(C₁₋₃-alkyl)₂,    or-   A and Z together with the atoms to which they are attached form a    saturated 5- or 6-membered heterocyclic ring which contains 1 or 2    identical or different heteroatoms or hetero groups selected from    the group consisting of O, S, —NH—, and —N(C₁₋₃-alkyl),-   X represents —CH═ or ═N—,-   E represents —NO₂ or CN.

Specifically, the following compounds may be mentioned:

Particular emphasis is given to the compounds

Particular emphasis is furthermore given to the compounds

Spinosyns which may be mentioned here are, in particular, spinosyns Aand D

as described in Boeck et al. in EP-375 316 A1 and Deamicis et al. in WO97/00265 A1.

Here, spinosyns are also understood as including synthetic andsemisynthetic derivatives of natural spinosyns or derivatives obtainedfrom genetically modified strains of; for example, Saccharopolysporaspecies, as described, for example, in WO 02/77004 and WO 02/77005.

By way of example, compounds of the formulae (IV) and (V) may bementioned in which R₃ is a glycoside (R₃═R₁), R₄ is H, OH or alkoxy; R₅is H, methyl, R₆ and R₇ are H or combined to a double bond or an epoxygroup, R₈ in formula (IV) is trans-1-butenyl, 1,3-butadienyl, butyl,3-hydroxybutenyl, propyl, 1-propenyl, 1,2epoxy-1-butyl, 3-oxo-1-butenyl,CH₃CH(OCH₃)CH═CH—, CH₃CH═CHCH(CH₂CO₂CH₃)—, or CH₃CH═CHCH[CH₂CON(CH₃)]—;R₉ is H or a glycoside (R₉═R₂).

Phenylpyrazoles which may be mentioned are, for example, the followingcompounds:

and compounds from WO 98/45274 for example of the type

Carbamates which may be mentioned are substituted phenyl carbamates andnaphthyl carbamates, preferred examples being:

-   -   2-oxobutylphenyl N-methylcarbamate,    -   4-dimethylamino-3-methylphenyl N-methylcarbamate,    -   2-isopropoxyphenyl N-methylcarbamate,    -   1-naphthyl N-methylcarbamate,    -   m-tolyl N-methylcarbamate,    -   3,4-xylyl N-methylcarbamate,    -   3,5-xylyl N-methylcarbamate,    -   2-[1,3-dioxolan-2-yl]phenyl N-methylcarbamate.

Phosphoric acid esters which may be mentioned as being preferred are thecompounds having the common names phoxim, fenitrothion, dichlorvos,trichlorfon and malathion.

Juvenile hormones and juvenile-hormone-like compounds are, for example,the following:

Substituted diaryl ethers are, for example, the following compounds:

R¹ R³ R⁵ R⁶ Z H H CH₃ 2-Cl O 5-F H CH₃ H O H H CF₃ H O H H C₂H₅ H O H HH H O H H CH₃ H CH₂ H H CH₃ H C(CH₃)₂

Benzoylureas are, for example, the following compounds:

R¹ R² R⁴ H Cl CF₃ Cl Cl CF₃ F F CF₃ H F CF₃ H Cl SCF₃ F F SCF₃ H F SCF₃H Cl OCF₃ F F OCF₃ H F OCF₃ F F

F F

F F

Triazines are, for example, the following compounds:

R¹ R² R³ cyclopropyl H H cyclopropyl H CH₃ cyclopropyl H C₂H₅cyclopropyl H C₃H₇-n cyclopropyl H C₄H₉-n cyclopropyl H C₅H₁₁-ncyclopropyl H C₆H₁₃-n cyclopropyl H C₇H₁₅-n cyclopropyl H C₈H₁₇-ncyclopropyl H C₁₂—H₂₅-n cyclopropyl H CH₂—C₄H₉-n cyclopropyl HCH₂CH(CH₃)C₂H₅ cyclopropyl H CH₂CH═CH₂ cyclopropyl Cl C₂H₅ cyclopropylCl C₆H₁₃-n cyclopropyl Cl C₈H₁₇-n cyclopropyl Cl C₁₂H₂₅-n cyclopropyl Hcyclopropyl cyclopropyl H COCH₃ cyclopropyl H COCH₃ HCl cyclopropyl HCOC₂H₅ HCl cyclopropyl H COC₂H₅ cyclopropyl H COC₃H₇-n cyclopropyl HCOC₃H₇-i cyclopropyl H COC₄H₉-t HCl cyclopropyl H COC₄H₉-n cyclopropyl HCOC₆H₁₃-n cyclopropyl H COC₁₁—H₂₃-n cyclopropyl COCH₃ COC₂H₅ cyclopropylCOC₃H₇-n COC₆H₁₃-n cyclopropyl COCH₃ COC₃H₇-n cyclopropyl COC₂H₅COC₃H₇-n cyclopropyl H COcyclopropyl cyclopropyl COcyclopropylCOcyclopropyl cyclopropyl COCH₃ COCH₃ isopropyl H H isopropyl H COCH₃isopropyl H COC₃H₇-n cyclopropyl H CONHCH₃ cyclopropyl H CONHC₃H₇-icyclopropyl CONHCH₃ CONHCH₃ cyclopropyl H SCNHCH₃ cyclopropyl HCONHCH₂CH═CH₂ cyclopropyl CONHCH₂CH═CH₂ CONHCH₂CH═CH₂ cyclopropylCSNHCH₃ CSNHCH₃

Here, particular mention may be made of cyromazine and dicylanil.

The amounts of the active combination compounds which, if appropriate,may be employed in addition to the pyrethrins/pyrethroids can be variedwithin wide limits from 0.05 to 25%, where the amounts in the range offrom 0.1 to 15.0% are particularly preferred and the amounts in therange of from 0.5 to 10.0% are very particularly preferred. Here,percentages are to be understood as percentages by weight, based on thefinished preparation.

Particular preference is given to combinations of the pyrethroids andpyrethrins, in particular α-cyanopyrethroids, preferably flumethrin,cyfluthrin and β-cyfluthrin, with neonicotinoids, in particularimidacloprid, thiamethoxam, clothianidin, nitenpyram, acetamiprid andthiacloprid, or with spinosyns, in particular spinosad.

Of course, it is possible to add further synergists such as piperonylbutoxide, tributyl phosphite and sesame oil to the preparationsaccording to the invention. These synergists are described, for example,in EP-A 413 610.

Stabilizers and antioxidants which may be mentioned are sulphites ormetabisulphites, such as potassium metabisulphite; organic acids, suchas citric acid, ascorbic acid; phenols, butylhydroxytoluene,butylhydroxyanisole, tocopherol. Preference is given to the organicacids citric acid and malic acid. Very particularly preferredstabilizers are citric acid and butylhydroxytoluene. Their proportionmay be varied widely in the range of from 0.05 to 2.5% by weight,particular preference being given to amounts in the range of from 0.075to 0.15% by weight. In spray formulations, the lower limit of thecustomary concentrations is lower, in general about 0.01% by weight;preferably, in spray formulations, the concentrations are from 0.03 to0.1% by weight.

To prepare the preparations according to the invention, it is possibleto use aromatic alcohols, such as benzyl alcohol, cyclic carbonates,such as propylene carbonate and ethylene carbonate, pyrrolidones, suchas pyrrolid-2-one, N-methylpyrrolidone, N-octylpyrrolidone,N-butylpyrrolidone, low-boiling alcohols, such as isopropanol, ethanol,higher alcohols, such as N-octyl alcohol, lanolin alcohol and n-butanol,cyclic and acyclic ketones, such as acetone, methyl ethyl ketone andcyclohexanone, glycols, such as ethylene glycol and propylene glycol,aliphatic cyclic or acyclic ethers, such as tetrahydrofurfuryl alcohol,diethylene glycol monoethyl ether, dipropylene glycol monopropyl etherand glycofurol, aliphatic or aromatic fatty acid esters, such asisopropyl myristate, isopropyl palmitate and benzyl benzoate,triglycerides based on oleic acid, palmitic acid, linoleic acid, stearicacid, caprylic acid and caprinic acid, lactones, such as butyrolactone,and their mixtures with one another. Particular preference is given tousing carbonates, alcohols and pyrrolidones.

The proportion of solvent in the compositions according to the inventiondepends, of course, on the type and amount of the further constituents,and accordingly, it may vary considerably. Usually, the solvent contentis at least 10% by weight, preferably at least 50% by weight,particularly preferably at least 60% by weight.

Furthermore, the formulations according to the invention may comprisepolymeric and/or oligomeric surface-active neutral, cationic or anionicauxiliaries, such as polyvinylpyrrolidone, polyvinyl alcohol,polyoxyethylene or polyoxypropylene sorbitan acid esters,polyoxyethylene stearates or products of the reaction of thephenoxyphenols and/or methoxysilanes with ethylene oxide and propyleneoxide, alkali metal and alkaline earth metal salts of the carboxylic andsulphonic acids, quaternary ammonium salts, such as benzylammoniumchloride—if appropriate also in combination with one another—in amountsof from 0.1 to 5% by weight, preferably from 0.2 to 2.0% by weight, toimprove flowability, viscosity and affinity to hair and fur.

Odour-masking agents are, for example, mixtures of organic fatty acidesters. In the formulations according to the invention, they arepreferably present in amounts of from 0.1 to 2% by weight.

If the compositions according to the invention are used in the form ofan aerosol spray, a presolution is, together with a propellant, filledinto customary spray cans or the like. Customary propellants orpropellant gases are, for example, gaseous hydrocarbons, such aspropane, butane (preference is given to a propane/butane mixture, inparticular in a ratio of 80:20), fluorocarbons, chlorofluorocarbons,N₂O, CO₂, nitrogen.

Surprisingly, the liquid formulations according to the invention have anexcellent storage stability of several years in all climate zones, andexcellent skin friendliness and user compatibility and environmentalcompatibility. Surprisingly, they are also highly suitable for beingfilled into and sold in storage-critical single dose plastic tubes whichusually consist of polypropylene, have a wall thickness of 300-500 μmand a filling volume of 1.0 to 4.0 ml.

Such single dose plastic tubes filled with the compositions according tothe invention accordingly also form part of the subject-matter of thepresent invention.

Additionally, the liquid formulations according to the invention have anunexpected synergistic, i.e. activity-enhancing, effect whenpyrethroids/pyrethrins are used as active compound.

The compositions according to the invention are environmentally friendlyand, owing to their very low toxicity, user-friendly.

Having favourable homeotherm toxicity, the compositions according to theinvention are suitable for controlling parasitic insects, in particularfleas and ticks, encountered on animals, in particular homeotherms,particularly preferably mammals. These animals may be domestic animalsand useful animals and also zoo animals, laboratory animals, testanimals and pets. The compositions according to the invention are activeagainst all or individual stages of development of the pests and againstresistant and normally sensitive test species.

The pests include:

from the order of the Anoplura, for example, Haematopinus spp.,Linognathus spp., Solenopotes spp., Pediculus spp., Pthirus spp.;

from the order of the Mallophaga, for example, Trimenopon spp., Menoponspp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicolaspp., Damalinea spp., Bovicola spp;

from the order of the Diptera, suborder Brachycera, for example,Chrysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp.,Haematobosca spp., Haematobia spp., Stomoxys spp., Fannia spp., Glossinaspp., Lucilia spp., Calliphora spp., Auchmeromyia spp., Cordylobia spp.,Cochliomyia spp., Chrysomyia spp., Sarcophaga spp., Wohlfartia spp.,Gasterophilus spp., Oesteromyia spp., Oedemagena spp., Hypoderma spp.,Oestrus spp., Rhinoestrus spp., Melophagus spp., Hippobosca spp.from the order of the Diptera, suborder Nematocera, for example, Culexspp., Aedes spp., Anopheles spp., Culicoides spp., Phlebotomus spp.,Simulium spp.from the order of the Siphonaptera, for example, Ctenocephalides spp.,Echidnophaga spp., Ceratophyllus spp., Pulex spp.from the order of the Metastigmata, for example, Hyalomma spp.,Rhipicephalus spp., Boophilus spp., Amblyomma spp., Haemaphysalis spp.,Dermacentor spp., Ixodes spp., Argas spp., Ornithodorus spp., Otobiusspp.;from the order of the Mesostigmata, for example, Dermanyssus spp.,Ornithonyssus spp., Pneumonyssus spp.from the order of the Prostigmata, for example, Cheyletiella spp.,Psorergates spp., Myobia spp., Demodex spp., Neotrombicula spp.;from the order of the Astigmata, for example, Acarus spp., Myocoptesspp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp.,Notoedres spp., Knemidocoptes spp., Neoknemidocoptes spp., Cytoditesspp., Laminosioptes spp.

Particular emphasis may be given to the action against Siphonaptera, inparticular against fleas and ticks.

The useful and breeding animals include mammals, such as, for example,cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys,rabbits, fallow deer, reindeer, fur-bearing animals, such as, forexample, mink, chinchilla, raccoon, birds, such as, for example, hens,geese, turkeys, ducks.

The laboratory animals and test animals include mice, rats, guinea pigs,golden hamsters, dogs and cats.

The pets include dogs and cats.

Particular emphasis is given to application on cat and dog.

Application can take place both prophylactically and therapeutically.

In principle, the novel liquid formulations according to the inventionare suitable for spot-on, pour-on and pump spray and also aerosol sprayapplications. The preferred application forms are pour-on and pumpspray. The spot-on application is very particularly preferred.

To prepare the liquid formulation according to the invention,appropriate amounts of the desired components are mixed with one anotherusing, for example, conventional stirring tanks or other suitableapparatus.

If required for the ingredients, the operations can also be carried outunder a protective atmosphere or by other methods where oxygen isexcluded.

The examples below serve to illustrate the invention:

EXAMPLES Example 1a

A homogeneous spot-on formulation (100 ml) comprising

1.00 g flumethrin 10.00 g imidacloprid 40.00 g MGK 264 48.00 gN-methylpyrrolidone//THFA (tetrahydrofurfuryl alcohol) (70:30) 0.10 gcitric acid 0.10 g BHT (butylhydroxytoluene)

Example 1b

A homogeneous spot-on formulation (100 ml) comprising

0.50 g flumethrin 10.00 g imidacloprid 40.00 g MGK 264 48.50 gN-methylpyrrolidone//THFA (tetrahydrofurfuryl alcohol) (70:30) 0.10 gcitric acid 0.10 g BHT (butylhydroxytoluene)

Example 2a

A homogeneous spot-on formulation (100 ml) comprising

0.50 g flumethrin 10.00 g imidacloprid 10.00 g MGK 264 59.40 gN-methylpyrrolidone//THFA (tetrahydrofurfuryl alcohol) (70:30) 25.00 gMiglyol 812 0.10 g citric acid 0.10 g BHT (butylhydroxytoluene)

Example 2b

A homogeneous spot-on formulation (100 ml) comprising

0.35 g flumethrin 10.00 g imidacloprid 10.00 g MGK 264 59.55 gN-methylpyrrolidone//THFA (tetrahydrofurfuryl alcohol) (70:30) 25.00 gMiglyol 812 0.10 g citric acid 0.10 g BHT (butylhydroxytoluene)

Example 2c

A homogeneous spot-n formulation (100 ml) comprising

0.20 g flumethrin 10.00 g imidacloprid 10.00 g MGK 264 59.70 gN-methylpyrrolidone//THFA (tetrahydrofurfuryl alcohol) (70:30) 25.00 gMiglyol 812 0.10 g citric acid 0.10 g BHT (butylhydroxytoluene)

Example 3

A homogeneous spot-on formulation (100 ml) comprising

0.50 g flumethrin 10.00 g imidacloprid 20.00 g MGK 264 50.00 gN-methylpyrrolidone//propylene carbonate (70:30) 13.75 g Miglyol 812 0.1g citric acid 0.1 g BHT (butylhydroxytoluene)

Example 4

A homogeneous spot-on formulation (100 ml) comprising

0.50 g flumethrin 10.00 g imidacloprid 10.00 g MGK 264 72.85 g benzylalcohol 14.48 g propylene carbonate 0.1 g citric acid 0.1 g BHT(butylhydroxytoluene)

Example 5

A homogeneous spot-on formulation (100 ml) comprising

0.35 g flumethrin 10.00 g imidacloprid 10.00 g MGK 264 72.70 g benzylalcohol 14.33 g propylene carbonate 0.1 g citric acid 0.1 g BHT(butylhydroxytoluene)

Example 6

A homogeneous spot-on formulation (100 ml) comprising

0.35 g flumethrin 10.00 g imidacloprid 15.00 g MGK 264 65.46 g benzylalcohol 12.94 g propylene carbonate 0.1 g citric acid 0.1 g BHT(butylhydroxytoluene) 5.00 g water

Example 7

A homogeneous spot-on formulation (100 ml) comprising

0.35 g flumethrin 10.00 g imidacloprid 15.00 g MGK 264 44.98 gN-methylpyrrolidone 32.08 g THFA 0.1 g citric acid 0.1 g BHT(butylhydroxytoluene)

In addition to the particularly preferred spot-on application, apreferred distribution of the active compound combinations mentioned byspraying using a pump spray or aerosol spray is also possible. For thispurpose, other formulations are required, which are described in thepreparation examples below.

Example 8

A pump spray formulation (250 ml) comprising

2.50 g imidacloprid 0.125 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.125g citric acid 20.80 g benzyl alcohol 4.125 g propylene carbonate 25.00 gwater 154.63 g isopropanol

For application of the formulation in the activity studies on dogs andcats, a conventional pump spray nozzle with D(v0.5) of about 65 μm wasused.

Example 9

A pump spray formulation (250 ml) comprising

2.50 g imidacloprid 0.125 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.125g citric acid 20.80 g benzyl alcohol 4.125 g propylene carbonate 25.00 gwater 154.63 g isopropanol

For application of the formulation in the activity studies on dogs andcats, a conventional pump spray nozzle with D(v0.5) of about 65 μm wasused.

Example 10a

A pump spray formulation (250 ml) comprising

2.50 g thiamethoxam 0.125 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.125g citric acid 20.80 g benzyl alcohol 4.125 g propylene carbonate 25.00 gwater 154.63 g isopropanol

For application of the formulation in the activity studies on dogs andcats, a conventional pump spray nozzle with D(v0.5) of about 65 μm wasused.

Example 10b

A pump spray formulation (250 ml) comprising

2.50 g thiacloprid 0.125 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.125 gcitric acid 20.80 g benzyl alcohol 4.125 g propylene carbonate 25.00 gwater 154.63 g isopropanol

For application of the formulation in the activity studies on dogs andcats, a conventional pump spray nozzle with D(v0.5) of about 65 μm wasused.

Example 11

A 250 ml presolution for preparing customary aerosol sprays, comprising

2.00 g thiamethoxam 0.15 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.025 gcitric acid 36.475 g benzyl alcohol 7.225 g propylene carbonate 25.00 gwater 141.25 g isopropanol140 g of the presolution according to Example II and 60 g of apropane/butane propellant mixture (propane:butane=80:20) were filledinto a conventional tin plate aerosol can, which was fitted with acustomary aerosol nozzle from Kosmos and then used for carrying outactivity studies on dogs and cats.

Example 12

A 250 ml presolution for preparing customary aerosol sprays, comprising

2.00 g imidacloprid 0.15 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.025 gcitric acid 36.475 g benzyl alcohol 7.225 g propylene carbonate 25.00 gwater 141.25 g isopropanol140 g of the presolution according to Example 12 and 60 g of apropane/butane propellant mixture (propane:butane=80:20) were filledinto a conventional tin plate aerosol can, which was fitted with acustomary aerosol nozzle from Kosmos and then used for carrying outactivity studies on dogs and cats.

Example 13

A 250 ml presolution for preparing customary aerosol sprays, comprising

2.00 g thiacloprid 0.15 g flumethrin 5.00 g MGK 264 0.125 g BHT 0.025 gcitric acid 36.475 g benzyl alcohol 7.225 g propylene carbonate 25.00 gwater 141.25 g isopropanol140 g of the presolution according to Example 13 and 60 g of apropane/butane propellant mixture (propane:butane=80:20) were filledinto a conventional tin plate aerosol can, which was fitted with acustomary aerosol nozzle from Kosmos and then used for carrying outactivity studies on dogs and cats.

The aerosol nozzle from Kosmos used in Examples 11-13 is used forpreparing commercial insecticide-containing aerosol sprays (for exampleBolfo Flohschutz Spray, Bolfo Plus Spray from Bayer HealthCare AGD-51368 Leverkusen).

Further laboratory tests on the activity against ticks according toExamples 1, 2, 5 and 9 show that the above formulation according to theinvention is highly active against ticks, is distinguished by itscompatibility with target animal and user and suitable for controllingfleas and ticks on small animals.

A. Activity Against Fleas on Dogs

Ctenocephalides felis

On days −4 and −1, dogs are infested with about 100 adult unfedCtenocephalides felis per dog. The fleas are placed on the neck of theanimal.

On day 0, the success of the infestation on the dog is examined bychecking the awake animal for fleas. The number of live fleas is noted.

After the fleas have been counted, the animals are treated. The dogs ofthe control group are not treated. The medicaments to be examined areadministered to the animals dermally as a spot-on in an application rateof 0.1 ml/kg of body weight or as a spray in an application rate of1-1.5 ml/kg of body weight. The application is carried out once on day0. Only animals that are clinically healthy are used.

On day 1 and on day 2, all dogs are examined for live fleas. The resultsare noted with the crude data.

On days 7, 14, 21 and 28, all dogs are reinfested with about 100 adultunfed Ctenocephalides felis per dog. In each case one day after thereinfestation, all dogs are checked for live fleas. The results arenoted with the crude data.

A formulation is considered to be highly active if, on day 1 and in eachcase on the second day after reinfestation, an efficacy of >95% isfound, and this action persists for at least 3-4 weeks.

The efficacy is calculated using a modified formula according to Abbott:

${{Efficacy}\%} = {\frac{\begin{matrix}{{\phi\mspace{11mu}{number}\mspace{14mu}{of}{\mspace{11mu}\;}{fleas}\mspace{14mu}{CG}} -} \\{\phi\mspace{14mu}{number}{\;\mspace{11mu}}{of}{\mspace{11mu}\;}{fleas}\mspace{14mu}{TG}}\end{matrix}}{\phi\mspace{14mu}{number}{\mspace{11mu}\;}{of}\mspace{14mu}{fleas}\mspace{11mu}{CG}} \times 100}$CG: Control groupTG: Treatment group

The medicaments of Formulation Examples 1 to 5, applied as a spot-on ata dosage of 0.1 ml/kg, were found to be highly effective againstCtenocephalides felis.

The medicaments of Formulation Examples 8 to 10, applied as a spray at adosage of 1-1.5 ml/kg, were found to be highly effective againstCtenocephalides felis.

B. Efficacy Against Ticks (Rhipicefalus sanguineus, Haemaphysalisleachi) on Dogs

In each case on days −4 and −1, dogs are sedated using 2% Rompun® (BayerAG, active compound: xylazine hydrochloride) (0.1 ml/kg of body weight).Once all dogs have been sedated (after about 10-15 minutes), they aretransferred to transport boxes, and 50 Rhipicefalus sanguineus orHaemaphysalis leachi (25♀. 25♂) per dog are applied to the neck of theanimal. After about ½ hours, the animals are retransferred from thetransport box into the cage.

On day 0, the success of the infestation on the dog is examined bychecking the awake animal for ticks. An intensive search is carried outin the region of the head and the ears, including the folds of the ears,in the region of the neck, on the lower abdomen, on the lower breast, onthe flank and in between the toes and the limbs. The number of suckinglive ticks is noted. Dead ticks are removed.

After the ticks have been counted, the animals are treated. The dogs ofthe control group are not treated. The medicaments to be examined areadministered to the animals dermally, as a spot-on, at 0.1 ml/kg of bodyweight or as a spray at 1-1.5 ml/kg of body weight. Application iscarried out once on day 0. Only animals which are clinically healthy areused.

On day 1 and on day 2, all dogs are checked for living and dead suckingticks. The results are noted with the crude data. On day 2, all livingand dead ticks are removed from the dog.

On days 7, 14, 21 and 28, all dogs are reinfested with in each case 50Rhipicefalus sanguineus or Haemaphysalis leachi (25♀, 25♂) per dog. Ineach case two days after the reinfestation, all dogs are checked forliving and dead sucking ticks. The results are noted with the crudedata. On the second day after the reinfestation, all living and deadticks are removed from the dog.

A formulation is considered to be highly active if, on day 2 and in eachcase on the second day after reinfestation, an efficacy of >90% isfound, and this action persists for at least 3 weeks.

For calculating the efficacy, a modified formula according to Abbott isused:

${{Efficacy}\%} = {\frac{\begin{matrix}{{\phi\mspace{14mu}{number}\mspace{14mu}{of}\mspace{14mu}{ticks}\mspace{14mu}{CG}} -} \\{\phi\mspace{14mu}{number}\mspace{14mu}{of}{\mspace{11mu}\;}{ticks}\mspace{14mu}{TG}}\end{matrix}}{\phi\mspace{14mu}{number}\mspace{14mu}{of}\mspace{14mu}{ticks}\mspace{14mu}{CG}} \times 100}$CG: Control groupTG: Treatment group

The medicaments according to Formulation Examples 1 to 5, applied as aspot-on at a dosage of 0.1 ml/kg, were found to be highly effectiveagainst Rhipicephalus sanguineus.

The medicaments according to Formulation Examples 8 to 10, applied as aspray at a dosage of 1-1.5 ml/kg, were found to be highly effectiveagainst Rhipicephalus sanguineus and Haemaphysalis leachi.

C. Activity Against Fleas (Ctenocephalides felis) on Cats

On day −1, cats are infested with about 100 adult unfed Ctenocephalidesfelis per cat. The fleas are placed onto the neck of the animal.

On day 0, the success of the infestation on the cat is examined bychecking the awake animal for fleas. The number of live fleas is noted.

After the fleas have been counted, the animals are treated. The cats ofthe control group are not treated. The medicaments to be examinedaccording to Examples 1 to 4 are administered to the animals dermally asa spot-on in an application rate of 0.1 ml/kg of body weight. Theapplication is carried out once on day 0. Only animals that areclinically healthy are used.

On day 2, all cats are examined for live fleas. The results are notedwith the crude data.

On days 6, 13, 20 and 27, all cats are reinfested with about 100 adultunfed Ctenocephalides felis. In each case two days after thereinfestation, all cats are checked for live fleas. The results arenoted with the crude data.

A formulation is considered to be highly active if, on day 2 and in eachcase on the second day after reinfestation, an efficacy of >95% isfound, and this action persists for at least 34 weeks.

The efficacy is calculated using a modified formula according to Abbott:

${{Efficacy}\%} = {\frac{\begin{matrix}{{\phi\mspace{11mu}{number}\mspace{14mu}{of}{\mspace{11mu}\;}{fleas}\mspace{14mu}{CG}} -} \\{\phi\mspace{14mu}{number}{\;\mspace{11mu}}{of}{\mspace{11mu}\;}{fleas}\mspace{14mu}{TG}}\end{matrix}}{\phi\mspace{14mu}{number}{\mspace{11mu}\;}{of}\mspace{14mu}{fleas}\mspace{11mu}{CG}} \times 100}$CG: Control groupTG: Treatment group

The medicaments of Formulation Examples 1 to 5, applied as a spot-on ata dosage of 0.1 ml/kg, were found to be highly effective againstCtenocephalides felis.

D. Activity Against Ticks (Haemaphysalis leachi) on Cats

In each case on day −2, cats are sedated using a mild sedative(acepromazine maleat). Once all cats have been sedated (after about10-15 minutes), 30 Haemaphysalis leachi (15♀, 15§) are applied to theneck of each animal.

On day −1, the success of the infestation on the cats is examined bychecking the awake animals for ticks. An intensive search is carried outin the region of the head and the ears, in the region of the neck, onthe lower abdomen, on the lower breast, on the flank and on the limbs.The number of sucking live ticks is noted. Dead ticks are removed.

After the ticks have been counted, the animals are divided into groups.Treatment is carried out on day 0. The cats of the control group are nottreated. The medicaments to be examined are administered to the animalsdermally as a spot-on at 0.1 ml/kg of body weight. Application iscarried out once on day 0. Only animals which are clinically healthy areused.

On day 2, all cats are checked for living and dead sucking ticks. Theresults are noted with the crude data. All living and dead ticks areremoved from the cat.

On days 6, 13, 20 and 27, all cats are reinfested with in each case 30Haemaphysalis leachi (15♀, 15♂) per cat. In each case two days after thereinfestation, all cats are checked for living and dead sucking ticks.The results are noted with the crude data. On the second day after thereinfestation, all living and dead ticks are removed from the cat.

A formulation is considered to be highly active if, on day 2 and in eachcase on the second day after reinfestation, an efficacy of >90% isfound, and this action persists for at least 3 weeks.

For calculating the efficacy, a modified formula according to Abbott isused:

${{Efficacy}\%} = {\frac{\begin{matrix}{{\phi\mspace{14mu}{number}\mspace{14mu}{of}\mspace{14mu}{ticks}\mspace{14mu}{CG}} -} \\{\phi\mspace{14mu}{number}\mspace{14mu}{of}{\mspace{11mu}\;}{ticks}\mspace{14mu}{TG}}\end{matrix}}{\phi\mspace{14mu}{number}\mspace{14mu}{of}\mspace{14mu}{ticks}\mspace{14mu}{CG}} \times 100}$CG: Control groupTG: Treatment group

The medicaments according to Formulation Examples 1 to 4, applied as aspot-on at a dosage of 0.1 ml/kg, were found to be highly effectiveagainst Haemaphysalis leachi.

E. Activity Against Fleas and Ticks Over a Period of 4 to 5 Weeks

The activity of the compositions according to the invention againstfleas and ticks was tested over a period of four to five weeks. The testwas carried out analogously to the description given under items A to D.

TABLE 1 Activity of the compositions of Examples 1a and 1b against fleasand ticks on dogs 1st 2nd Week 0 3rd Week 1 4th Week 2 Infes- Infes-Appl. d 1 d 2 Infes- d 9 Infes- d 16 tation: tation: d 0 Vol. efficacyefficacy tation: efficacy tation: efficacy Day −4 Day −1 Treatment ml/kgCF % RS % CF % RS % Day 7 CF % RS % Day 14 CF % RS % Example 1a 0.10 10081 100 94 100 100 100 100 Example 1b 0.10 100 67 100 94 100 96 100 995th Week 3 6th Week 4 7th Week 5 Appl. Infes- d 23 Infes- d 30 Infes- d37 d 0 Vol. tation: efficacy tation: efficacy tation: efficacy Treatmentml/kg Day 21 CF % RS % Day 28 CF % RS % Day 35 CF % RS % Example 1a 0.10100 98 97 100 95 95 Example 1b 0.10 100 100 98 99 92 98 Appl. Vol. =Volume applied in ml/kg of body weight CF % = Activity againstCtenocephalides felis fleas in %, calculated by determination of thegeometrical mean compared to an untreated control group RS % = Activityagainst Rhipicephalus sanguineus ticks in %, calculated by determinationof the geometrical mean compared to an untreated control group d = Day

TABLE 2 Activity of the compositions of Examples 2a, 2b and 2c againstfleas and ticks on dogs 1st 2nd Week 0 3rd Week 1 4th Week 2 Infes-Infes- Appl. d 1 d 2 Infes- d 8 d 9 Infes- d 16 tation: tation: d 0 Vol.efficacy efficacy tation: efficacy efficacy tation: efficacy Day −4 Day−1 Treatment ml/kg CF % RS % CF % RS % Day 7 CF % RS % CF % RS % Day 14CF % RS % Example 2a 0.10 93 72 100 94 100 100 100 100 99 99 Example 2b0.10 96 61 100 90 100 97 99 98 94 92 Example 2c 0.10 98 60 100 98 100100 100 99 97 94 5th Week 3 6th Week 4 7th Week 5 Appl. Infes- d 23Infes- d 30 Infes- d 37 d 0 Vol. tation: efficacy tation: efficacytation: efficacy Treatment ml/kg Day 21 CF % RS % Day 28 CF % RS % Day35 CF % RS % Example 2a 0.10 100 100 79 90 83 89 Example 2b 0.10 75 8556 77 13 33 Example 2c 0.10 94 95 84 82 58 54 Appl. Vol. = Volumeapplied in ml/kg of body weight CF % = Activity against Ctenocephalidesfelis fleas in %, calculated by determination of the geometrical meancompared to an untreated control group RS % = Activity againstRhipicephalus sanguineus ticks in %, calculated by determination of thegeometrical mean compared to an untreated control group d = Day

TABLE 3 Activity of the compositions of Examples 2b and 5 against fleasand ticks on cats 1st Week 0 2nd Week 1 3rd Week 2 Infes- Appl. d 2Infes- d 8 Infes- d 15 tation: d 0 Vol. efficacy tation: efficacytation: efficacy Day −2 Treatment ml/kg CF % HL % Day 7 CF % HL % Day 14CF % HL % Example 2b 0.10 100 35 100 67 97 86 Example 5 0.10 100 24 10093 100 91 4th Week 3 5th Week 4 Appl. Infes- d 23 Infes- d 29 d 0 Vol.tation: efficacy tation: efficacy Treatment ml/kg Day 21 CF % HL % Day28 CF % HL % Example 2b 0.10 91 80 84 71 Example 5 0.10 99 91 94 97Appl. Vol. = Volume applied in ml/kg of body weight CF % = Activityagainst Ctenocephalides felis fleas in %, calculated by determination ofthe geometrical mean compared to an untreated control group HL % =Activity against Haemaphysalis leachi ticks in %, calculated bydetermination of the geometrical mean compared to an untreated controlgroup d = Day

TABLE 4 Activity of the compositions of Example 9 against fleas andticks on dogs 1st 2nd 3rd 4th Infes- Infes- Week 0 Infes- Week 1 Infes-Week 2 tation: tation: d 0 Appl. Vol. d 2 ttaion: d 8 tation: d 14 Day−4 Day −1 Treatment ml/kg Parasite efficacy Day 7 efficacy Day 14efficacy Example 9 1.30 CF 100 100 100 HL 89 99 98 RS 87 99 100 5th 6th7th Infes- Week 3 Infes- Week 4 Infes- Week 5 d 0 Appl. Vol. tation: d21 tation: d 28 tation: d 35 Treatment ml/kg Parasite Day 21 efficacyDay 28 efficacy Day 35 efficacy Example 9 1.30 CF 100 100 100 HL 94 8974 RS 98 96 91 Appl. Vol. = Volume applied in ml/kg of body weight CF %= Activity against Ctenocephalides felis fleas in %, calculated bydetermination of the geometrical mean compared to an untreated controlgroup HL % = Activity against Haemaphysalis leachi ticks in %,calculated by determination of the geometrical mean compared to anuntreated control group RS % = Activity against Rhipicephalus sanguineusticks in %, calculated by determination of the geometrical mean comparedto an untreated control group d = Day

1. A composition comprising: a. flumethrin; and, b.(2-(2-ethylhexyl)-3a,4,7,7a-tetrahydro-4,7-methano-1H-isoindole-1,3(2H)-dionewherein the amount of b is at least 20 fold more than a.
 2. Thecomposition of claim 1, further comprising a neonicotinoid insecticide.3. The composition of claim 1, further comprising imidacloprid.
 4. Amethod for controlling parasites comprising applying to an animal inneed thereof an effective amount of a composition of claim 1.